Three aspects of alpha-fetoprotein (AFP) - the fetal protein associated with hepatoma, teratomas and some other tumors - will be studied. 1. Chemical characterization including sequencing will be continued. We have previously determined the partial amino acid sequence of human and bovine AFP and we are currently working on the whole amino acid sequence of bovine AFP. Peptides will be synthesized on the basis of sequence information from human AFP. 2. New immunoassays based on these peptides and their antibodies will be set up. Such an assay can, perhaps, be used to measure AFP in biological samples. This would eliminate the need for AFP purified from fetuses or hepatoma patients' sera. 3. Expression of AFP in spontaneous hepatomas and the application of AFP to immunotherapy and immunoprevention of AFP producing hepatomas will be studied. Recent demonstration of in vitro cytotoxicity of heterologous anti-AFP to AFP producing hepatoma cells and the fact that tolerance to AFP can be broken in experimental animals suggest that this may be possible. Initial studies have shown that mice having serum antibodies to AFP do not have increased resistance towards hepatomas. Current studies aim at evaluation of the effect of heterologous AFP antibodies, homologous antibodies produced by hybridomas, and conjugates of cytotoxic drugs to such antibodies on the development of hepatomas.